Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Author(s): Anishma Payyappilliparambil Narayanan, Jayalakshmi Jayan, Sachithra Thazhathuveedu Sudevan, Archana Dhyani, Subin Mary Zachariah* and Bijo Mathew*

DOI: 10.2174/1386207326666230731092409

DownloadDownload PDF Flyer Cite As
Flavonoid and Chalcone Scaffolds as Inhibitors of BACE1: Recent Updates

Page: [1243 - 1256] Pages: 14

  • * (Excluding Mailing and Handling)

Abstract

Flavonoids and chalcones are two major classes of chemical moieties that have a vast background of pharmacological activities. Chalcone is a subclass of flavonoids whose therapeutic potential has been implicated due to an array of bioactivities. A lot of research works have shown interest in investigating the neuroprotective effect of these molecules, and have revealed them to be much more potent molecules that can be used to treat neurodegenerative disorders. Beta-site APP cleaving enzyme (BACE1), which is majorly found in the brain, is one of the reasons behind the development of Alzheimer’s disease (AD). Flavonoids and chalcones have proven clinical data that they inhibit the production of Aβ plaques that are involved in the progression of AD. In this article, we have provided a detailed chronological review of the research work on the BACE1 inhibiting potency of both flavonoids and chalcones. Almost all the flavonoids and chalcones mentioned in this article have shown very good in vitro and in vivo BACE1 inhibiting activity. The docking studies and the structural importance of some BACE1-inhibiting flavonoids, as well as chalcones, are also mentioned here.

Graphical Abstract

[1]
Wang, T.; Li, Q.; Bi, K. Bioactive flavonoids in medicinal plants: Structure, activity and biological fate. Asian J. Pharma. Sci., 2018, 13(1), 12-23.
[http://dx.doi.org/10.1016/j.ajps.2017.08.004] [PMID: 32104374]
[2]
Mathew, B.; Suresh, J.; Mathew, G.; Rasheed, S.; Vilapurathu, J.; Jayaraj, P. Flavonoids: An outstanding structural core for the inhibition of xanthine oxidase enzyme. Curr. Enzym. Inhib., 2015, 11(2), 108-115.
[http://dx.doi.org/10.2174/1573408011666150730204108]
[3]
Panche, A.N. ADD and SRC. J. Nutr. Sci., 2017, 5, 1-15.
[4]
Bai, L.; Li, X.; He, L.; Zheng, Y.; Lu, H.; Li, J.; Zhong, L.; Tong, R.; Jiang, Z.; Shi, J.; Li, J. Antidiabetic potential of flavonoids from traditional chinese medicine: A review. Am. J. Chin. Med., 2019, 47(5), 933-957.
[http://dx.doi.org/10.1142/S0192415X19500496] [PMID: 31248265]
[5]
Jing, Z.; Jun, W.; Gei-Sheng, Z.; Ya-Jie, T.; Hui-Juan, T. Study of anti-amnesic effect and mechanismsof single and combined use of donepezil and ginko ketoester tablet on scopalamine-induced memory impairement in mice. Oxid. Med. Cell. Longev., 2019, 2019, 1-16.
[http://dx.doi.org/10.1155/2019/6138723]
[6]
Anand, P.; Singh, B. Synthesis and evaluation of novel carbamate-substituted flavanone derivatives as potent acetylcholinesterase inhibitors and anti-amnestic agents. Med. Chem. Res., 2013, 22(4), 1648-1659.
[http://dx.doi.org/10.1007/s00044-012-0162-3]
[7]
Rakesh, O.; Alakh, N.S.; Muruganandam, A.V.; Gireesh, K.S.; Sairam, K. Aspargus recemosus enhances memory and protects against amnesia in rodent models. Brain Cogn., 2010, 17(1), 1-9.
[8]
Richetti, S.K.; Blank, M.; Capiotti, K.M.; Piato, A.L.; Bogo, M.R.; Vianna, M.R.; Bonan, C.D. Quercetin and rutin prevent scopolamine-induced memory impairment in zebrafish. Behav. Brain Res., 2011, 217(1), 10-15.
[http://dx.doi.org/10.1016/j.bbr.2010.09.027] [PMID: 20888863]
[9]
Murata, K. Chemical diversity of β-secretase inhibitors from natural resources. SAGE J., 2019, 1-17.
[10]
Salehi, B.; Quispe, C.; Chamkhi, I.; El Omari, N.; Balahbib, A.; Sharifi-Rad, J.; Bouyahya, A.; Akram, M.; Iqbal, M.; Docea, A.O.; Caruntu, C.; Leyva-Gómez, G.; Dey, A.; Martorell, M.; Calina, D.; López, V.; Les, F. Pharmacological properties of chalcones: A review of preclinical including molecular mechanisms and clinical evidence. Front. Pharmacol., 2021, 11, 592654.
[http://dx.doi.org/10.3389/fphar.2020.592654] [PMID: 33536909]
[11]
Song, K.S.; Choi, S.H.; Hur, J.M.; Park, H.J.; Yang, E.J.; Inhee, M.J. Inhibitory effects of flavonoids isolated from leaves of Petasites japonicus on β-secretase (BACE1). Food Sci. Biotechnol., 2008, 17(6), 1165-1170.
[12]
Yin, F.; Liu, J.; Ji, X.; Wang, Y.; Zidichouski, J.; Zhang, J. Silibinin: A novel inhibitor of Aβ aggregation. Neurochem. Int., 2011, 58(3), 399-403.
[http://dx.doi.org/10.1016/j.neuint.2010.12.017] [PMID: 21185897]
[13]
Mathew, B.; Parambi, D.G.T.; Sivasankarapillai, V.S.; Uddin, M.S.; Suresh, J.; Mathew, G.E.; Joy, M.; Marathakam, A.; Gupta, S.V. Perspective design of chalcones for the management of CNS disorders: A mini-review. CNS Neurol. Disord. Drug Targets, 2019, 18(6), 432-445.
[http://dx.doi.org/10.2174/1871527318666190610111246] [PMID: 31187716]
[14]
Matos, M.J.; Vazquez-Rodriguez, S.; Uriarte, E.; Santana, L. Potential pharmacological uses of chalcones: A patent review (from June 2011 – 2014). Expert Opin. Ther. Pat., 2015, 25(3), 351-366.
[http://dx.doi.org/10.1517/13543776.2014.995627] [PMID: 25598152]
[15]
Mathew, B.; Oh, J.M.; Baty, R.S.; Batiha, G.S.; Parambi, D.G.T.; Gambacorta, N. Piperazine-substituted chalcones: A new class of neurological disorders. Environ. Sci. Poluut. Res., 2021, 28, 38855-38866.
[http://dx.doi.org/10.1007/s11356-021-13320-y] [PMID: 33743158]
[16]
Sahu, N.K.; Balbhadra, S.S.; Choudhary, J.; Kohli, D.V. Exploring pharmacological significance of chalcone scaffold: A review. Curr. Med. Chem., 2012, 19(2), 209-225.
[http://dx.doi.org/10.2174/092986712803414132] [PMID: 22320299]
[17]
Zhou, B.; Xing, C. Diverse Molecular Targets for Chalcones with Varied Bioactivities. Med. Chem. (Los Angeles), 2015, 5(8), 388-404.
[http://dx.doi.org/10.4172/2161-0444.1000291] [PMID: 26798565]
[18]
Haniu, M.; Denis, P.; Young, Y.; Mendiaz, E.A.; Fuller, J.; Hui, J.O.; Bennett, B.D.; Kahn, S.; Ross, S.; Burgess, T.; Katta, V.; Rogers, G.; Vassar, R.; Citron, M. Characterization of Alzheimer’s β-Secretase Protein BACE. J. Biol. Chem., 2000, 275(28), 21099-21106.
[http://dx.doi.org/10.1074/jbc.M002095200] [PMID: 10887202]
[19]
Mathew, B.; Koyimparambath, V.P.; Oh, J.M.; Khames, M.A.; Nair, A.S.; Nath, L.R. Trimethoxylated halogenated chalcones as dual inhibitors of MAO-B nad BACE-1 for treatment of neurodegenerative disorders. Pharmaceutics, 2021, 13, 1-16.
[20]
Hussain, I.; Powell, D.; Howlett, D.R.; Tew, D.G.; Meek, T.D.; Chapman, C.; Gloger, I.S.; Murphy, K.E.; Southan, C.D.; Ryan, D.M.; Smith, T.S.; Simmons, D.L.; Walsh, F.S.; Dingwall, C.; Christie, G. Identification of a novel aspartic protease (Asp 2) as β-secretase. Mol. Cell. Neurosci., 1999, 14(6), 419-427.
[http://dx.doi.org/10.1006/mcne.1999.0811] [PMID: 10656250]
[21]
Bennett, B.D.; Denis, P.; Haniu, M.; Teplow, D.B.; Kahn, S.; Louis, J.C.; Citron, M.; Vassar, R. A furin-like convertase mediates propeptide cleavage of BACE, the Alzheimer’s β -secretase. J. Biol. Chem., 2000, 275(48), 37712-37717.
[http://dx.doi.org/10.1074/jbc.M005339200] [PMID: 10956649]
[22]
Vassar, R.; Bennett, B.D.; Babu-Khan, S.; Kahn, S.; Mendiaz, E.A.; Denis, P.; Teplow, D.B.; Ross, S.; Amarante, P.; Loeloff, R.; Luo, Y.; Fisher, S.; Fuller, J.; Edenson, S.; Lile, J.; Jarosinski, M.A.; Biere, A.L.; Curran, E.; Burgess, T.; Louis, J.C.; Collins, F.; Treanor, J.; Rogers, G.; Citron, M. β-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science, 1999, 286(5440), 735-741.
[http://dx.doi.org/10.1126/science.286.5440.735] [PMID: 10531052]
[23]
Marcinkiewicz, M.; Seidah, N.G. Coordinated expression of β-amyloid precursor protein and the putative β-secretase BACE and alpha-secretase ADAM10 in mouse and human brain. J. Neurochem., 2000, 75(5), 2133-2143.
[http://dx.doi.org/10.1046/j.1471-4159.2000.0752133.x] [PMID: 11032903]
[24]
Ahmed, R.R.; Holler, C.J.; Webb, R.L.; Li, F.; Beckett, T.L.; Murphy, M.P. BACE1 and BACE2 enzymatic activities in Alzheimer’s disease. J. Neurochem., 2010, 112(4), 1045-1053.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06528.x] [PMID: 19968762]
[25]
Chen, J.; Wang, J.; Yin, B.; Pang, L.; Wang, W.; Zhu, W. Molecular Mechanism of Binding Selectivity of Inhibitors toward BACE1 and BACE2 Revealed by Multiple Short Molecular Dynamics Simulations and Free-Energy Predictions. ACS Chem. Neurosci., 2019, 10(10), 4303-4318.
[http://dx.doi.org/10.1021/acschemneuro.9b00348] [PMID: 31545898]
[26]
Chen, J.; Zhang, S.; Wang, W.; Sun, H.; Zhang, Q.; Liu, X. Binding of Inhibitors to BACE1 Affected by pH-Dependent Protonation: An Exploration from Multiple Replica Gaussian Accelerated Molecular Dynamics and MM-GBSA Calculations. ACS Chem. Neurosci., 2021, 12(14), 2591-2607.
[http://dx.doi.org/10.1021/acschemneuro.0c00813] [PMID: 34185514]
[27]
Cole, S.; Vassar, R. BACE1 structure and function in health and Alzheimer’s disease. Curr. Alzheimer Res., 2008, 5(2), 100-120.
[http://dx.doi.org/10.2174/156720508783954758] [PMID: 18393796]
[28]
Bennett, B.D.; Babu-Khan, S.; Loeloff, R.; Louis, J.C.; Curran, E.; Citron, M.; Vassar, R. Expression analysis of BACE2 in brain and peripheral tissues. J. Biol. Chem., 2000, 275(27), 20647-20651.
[http://dx.doi.org/10.1074/jbc.M002688200] [PMID: 10749877]
[29]
Yan, R.; Vassar, R. Targeting the β secretase BACE1 for Alzheimer’s disease therapy. Lancet Neurol., 2014, 13(3), 319-329.
[http://dx.doi.org/10.1016/S1474-4422(13)70276-X] [PMID: 24556009]
[30]
Sathya, M.; Premkumar, P.; Karthick, C.; Moorthi, P.; Jayachandran, K.S.; Anusuyadevi, M. BACE1 in Alzheimer’s disease. Clin. Chim. Acta, 2012, 414, 171-178.
[http://dx.doi.org/10.1016/j.cca.2012.08.013] [PMID: 22926063]
[31]
Zhao, J.; Liu, X.; Xia, W.; Zhang, Y.; Wang, C. Targeting amyloidogenic processing of APP in alzheimer’s disease. Front Mol. Nuerosci, 2020, 13, 137.
[32]
Malamas, M.S.; Barnes, K.; Johnson, M.; Hui, Y.; Zhou, P.; Turner, J.; Hu, Y.; Wagner, E.; Fan, K.; Chopra, R.; Olland, A.; Bard, J.; Pangalos, M.; Reinhart, P.; Robichaud, A.J. Di-substituted pyridinyl aminohydantoins as potent and highly selective human β-secretase (BACE1) inhibitors. Bioorg. Med. Chem., 2010, 18(2), 630-639.
[http://dx.doi.org/10.1016/j.bmc.2009.12.007] [PMID: 20045648]
[33]
Hunt, K.W.; Cook, A.W.; Watts, R.J.; Clark, C.T.; Vigers, G.; Smith, D.; Metcalf, A.T.; Gunawardana, I.W.; Burkard, M.; Cox, A.A.; Geck Do, M.K.; Dutcher, D.; Thomas, A.A.; Rana, S.; Kallan, N.C.; DeLisle, R.K.; Rizzi, J.P.; Regal, K.; Sammond, D.; Groneberg, R.; Siu, M.; Purkey, H.; Lyssikatos, J.P.; Marlow, A.; Liu, X.; Tang, T.P. Spirocyclic β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors: From hit to lowering of cerebrospinal fluid (CSF) amyloid β in a higher species. J. Med. Chem., 2013, 56(8), 3379-3403.
[http://dx.doi.org/10.1021/jm4002154] [PMID: 23537249]
[34]
Gabr, M.T.; Abdel-Raziq, M.S. Structure-based design, synthesis, and evaluation of structurally rigid donepezil analogues as dual AChE and BACE-1 inhibitors. Bioorg. Med. Chem. Lett., 2018, 28(17), 2910-2913.
[http://dx.doi.org/10.1016/j.bmcl.2018.07.019] [PMID: 30017317]
[35]
Evin, G.; Kenche, V.B. BACE Inhibitors as Potential Therapeutics for Alzheimer ’s disease. Recent Pat. CNS Drug Discov., 2007, 188-199.
[36]
Kandasamy, S.; Magudeeswaran, S.; Govindasamy, H.; Lakshmanan, M.; Poomani, K. Investigation of Intermolecular interactions and Stability of Verubecestat in the active site of BACE1: Development of First model from QM/MM based Charge density and MD Analysis. J. Biomol. Struct. Dyn., 2049, 37(7), 2339-2354.
[http://dx.doi.org/10.1080/07391102.2018.1479661] [PMID: 30044206]
[37]
Prati, F.; Bottegoni, G.; Bolognesi, M.L.; Cavalli, A. BACE-1 inhibitors: From recent single-target molecules to multitarget compounds for Alzheimer’s disease. J. Med. Chem., 2018, 61(3), 619-637.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00393] [PMID: 28749667]
[38]
Ghosh, A.K.; Osswald, H.L. BACE1 (β-secretase) inhibitors for the treatment of Alzheimer’s disease. Chem. Soc. Rev., 2014, 43(19), 6765-6813.
[http://dx.doi.org/10.1039/C3CS60460H] [PMID: 24691405]
[39]
Schneider, L.; Mangialasche, F.; Andreasen, N.; Feldman, H.; Giacobini, E.; Jones, R. Clinical trials and late-stage drug development for Alzheimer’s disease: An appraisal from 1984 to 2014. J. Inter. Med., 2014, 251-283.
[40]
Hu, X.; Das, B.; Hou, H.; He, W.; Yan, R. BACE1 deletion in the adult mouse reverses preformed amyloid deposition and improves cognitive functions. J. Exp. Med., 2018, 215(3), 927-940.
[http://dx.doi.org/10.1084/jem.20171831] [PMID: 29444819]
[41]
Liu, S.; Fu, R.; Cheng, X.; Chen, S.P.; Zhou, L.H. Exploring the binding of BACE-1 inhibitors using comparative binding energy analysis (COMBINE). BMC Struct. Biol., 2012, 12(1), 21.
[http://dx.doi.org/10.1186/1472-6807-12-21] [PMID: 22925713]
[42]
Wessels, A.M.; Voss, T.; Aisen, P.S.; Dupre, N.; Shering, C.; Lines, C. Cognitive outcomes in trials of two BACE inhibitors in Alzheime ’s disease. JAD, 2020, 1-10.
[43]
Naushad, M.; Durairajan, S.S.K.; Bera, A.K.; Senapati, S.; Li, M.; Li, M. Natural compounds with anti-BACE1 activity as promising therapeutic drugs for treating alzheimerʼs disease. Planta Med., 2019, 85(17), 1316-1325.
[http://dx.doi.org/10.1055/a-1019-9819] [PMID: 31618777]
[44]
Gu, T.; Wu, W.Y.; Dong, Z.X.; Yu, S.P.; Sun, Y.; Zhong, Y.; Lu, Y.T.; Li, N.G. Development and Structural Modification of BACE1 Inhibitors. Molecules, 2016, 22(1), 4.
[http://dx.doi.org/10.3390/molecules22010004] [PMID: 28025519]
[45]
Keith, D. Green MYF and SG-T. Multifunctional Donepezil Analogues as Cholinesterase and BACE1 Inhibitors. Molecules, 2018, 23, 1-22.
[46]
Woltering, T.J.; Wostl, W.; Hilpert, H.; Rogers-Evans, M.; Pinard, E.; Mayweg, A.; Göbel, M.; Banner, D.W.; Benz, J.; Travagli, M.; Pollastrini, M.; Marconi, G.; Gabellieri, E.; Guba, W.; Mauser, H.; Andreini, M.; Jacobsen, H.; Power, E.; Narquizian, R. BACE1 inhibitors: A head group scan on a series of amides. Bioorg. Med. Chem. Lett., 2013, 23(14), 4239-4243.
[http://dx.doi.org/10.1016/j.bmcl.2013.05.003] [PMID: 23735744]
[47]
Miranda, A.; Montiel, E.; Ulrich, H.; Paz, C. Selective Secretase Targeting for Alzheimer’s Disease Therapy. J. Alzheimers Dis., 2021, 81(1), 1-17.
[http://dx.doi.org/10.3233/JAD-201027] [PMID: 33749645]
[48]
Hsiao, C.C.; Rombouts, F.; Gijsen, H.J.M. New evolutions in the BACE1 inhibitor field from 2014 to 2018. Bioorg. Med. Chem. Lett., 2019, 29(6), 761-777.
[http://dx.doi.org/10.1016/j.bmcl.2018.12.049] [PMID: 30709653]
[49]
Jeon, S.Y.; Bae, K.; Seong, Y.H.; Song, K.S. Green tea catechins as a BACE1 (β-Secretase) inhibitor. Bioorg. Med. Chem. Lett., 2003, 13(22), 3905-3908.
[http://dx.doi.org/10.1016/j.bmcl.2003.09.018] [PMID: 14592472]
[50]
Mohamed Yusof, N.I.S.; Abdullah, Z.L.; Othman, N.; Mohd Fauzi, F. Structure-activity relationship analysis of flavonoids and its inhibitory activity against BACE1 enzyme toward a better therapy for alzheimer’s disease. Front Chem., 2022, 10, 874615.
[http://dx.doi.org/10.3389/fchem.2022.874615] [PMID: 35832462]
[51]
Tran, T.S.; Le, M.T.; Nguyen, T.C.V.; Tran, T.H.; Tran, T.D.; Thai, K.M. Synthesis, in silico and in vitro evaluation for acetylcholinesterase and BACE-1 inhibitory activity of some N-substituted-4-phenothiazine-chalcones. Molecules, 2020, 25(17), 3916.
[http://dx.doi.org/10.3390/molecules25173916] [PMID: 32867308]
[52]
Choi, Y.H.; Yon, G.H.; Hong, K.S.; Yoo, D.S.; Choi, C.W.; Park, W. In vitro BACE-1 inhibitory phenolic components from the seeds of psoralea corylifolia. Plant Meda, 2008, 4(11), 1405-8.
[53]
Zhu, Z.; Li, C.; Wang, X.; Yang, Z. State key laboratory of drug research, shanghai institute of materia medica, chinese academy of sciences, shanghai, China. J. Neurochem., 2010, 114, 374-385.
[54]
Jung, H.A.; Yokozawa, T.; Kim, B.W.; Jung, J.H.; Choi, J.S. Selective inhibition of prenylated flavonoids from Sophora flavescens against BACE1 and cholinesterases. Am. J. Chin. Med., 2010, 38(2), 415-429.
[http://dx.doi.org/10.1142/S0192415X10007944] [PMID: 20387235]
[55]
Kang, J.; Cho, J.; Curtis-Long, M.; Ryu, H.; Kim, J.; Kim, H.; Yuk, H.; Kim, D.; Park, K. Inhibitory evaluation of sulfonamide chalcones on β-secretase and acylcholinesterase. Molecules, 2012, 18(1), 140-153.
[http://dx.doi.org/10.3390/molecules18010140] [PMID: 23344193]
[56]
Park, S.H.; Yang, E.J.; Kim, S.I.; Song, K.S. β-Secretase (BACE1)-inhibiting C-methylrotenoids from Abronia nana suspension cultures. Bioorg. Med. Chem. Lett., 2014, 24(13), 2945-2948.
[http://dx.doi.org/10.1016/j.bmcl.2014.04.060]
[57]
Cox, C.J.; Choudhry, F.; Peacey, E.; Perkinton, M.S.; Richardson, J.C.; Howlett, D.R.; Lichtenthaler, S.F.; Francis, P.T.; Williams, R.J. Dietary (−)-epicatechin as a potent inhibitor of βγ-secretase amyloid precursor protein processing. Neurobiol. Aging, 2015, 36(1), 178-187.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.07.032] [PMID: 25316600]
[58]
Zou, Z.; Xu, P.; Zhang, G.; Cheng, F.; Chen, K.; Li, J. Selagintri flavonoids with BACE1 inhibitory activity from the fern Selaginella doederleinii. Phytochemistry, 2017, 134, 114-121.
[PMID: 27889245]
[59]
Yang, S.; Liu, W.; Lu, S.; Tian, Y.; Wang, W.; Ling, T.; Liu, R. A novel multifunctional compound camellikaempferoside B decreases Aβ production, Interferes with Aβ aggregation, and prohibits Aβ-mediated neurotoxicity and neuroinflammation. ACS Chem. Neurosci., 2016, 7(4), 505-518.
[http://dx.doi.org/10.1021/acschemneuro.6b00091] [PMID: 27015590]
[60]
Youn, K.; Yu, Y.; Lee, J.; Jeong, W.S.; Ho, C.T.; Jun, M. Polymethoxyflavones: novel β-secretase (BACE1) inhibitors from citrus peels. Nutrients, 2017, 9(9), 973.
[http://dx.doi.org/10.3390/nu9090973] [PMID: 28869548]
[61]
Ali, M.Y.; Jannat, S.; Edraki, N.; Das, S.; Chang, W.K.; Kim, H.C.; Park, S.K.; Chang, M.S. Flavanone glycosides inhibit β-site amyloid precursor protein cleaving enzyme 1 and cholinesterase and reduce Aβ aggregation in the amyloidogenic pathway. Chem. Biol. Interact., 2019, 309, 108707.
[http://dx.doi.org/10.1016/j.cbi.2019.06.020] [PMID: 31194956]
[62]
Youn, K.; Jun, M. Biological evaluation and docking analysis of potent BACE1 inhibitors from Boesenbergia rotunda. Nutrients, 2019, 11(3), 662.
[http://dx.doi.org/10.3390/nu11030662] [PMID: 30893825]
[63]
Ribaudo, G.; Coghi, P.; Zanforlin, E.; Law, B.Y.K.; Wu, Y.Y.J.; Han, Y.; Qiu, A.C.; Qu, Y.Q.; Zagotto, G.; Wong, V.K.W. Semi-synthetic isoflavones as BACE-1 inhibitors against Alzheimer’s disease. Bioorg. Chem., 2019, 87, 474-483.
[http://dx.doi.org/10.1016/j.bioorg.2019.03.034] [PMID: 30927588]
[64]
Prajapati, R.; Park, S.E.; Park, H.J.; Jung, H.A.; Choi, J.S. Identification of a Potent and Selective Human Monoamine Oxidase-A Inhibitor, Glycitein, an Isoflavone Isolated from Pueraria lobata Flowers. ACS Food Sci. Technol., 2021, 1(4), 538-550.
[http://dx.doi.org/10.1021/acsfoodscitech.0c00152]
[65]
Ahuja, A.; Tyagi, P.K.; Tyagi, S.; Kumar, A.; Kumar, M.; Sharifi-Rad, J. Potential of Pueraria tuberosa (Willd.) DC. to rescue cognitive decline associated with BACE1 protein of Alzheimer’s disease on Drosophila model: An integrated molecular modeling and in vivo approach. Int. J. Biol. Macromol., 2021, 179, 586-600.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.03.032] [PMID: 33705837]
[66]
Krishnendu, PR.; Vishal, PK.; Vaishnav, B.; Arjun, B; Subin, MZ Formulating the structural aspects of various benzimidazole cognates. Curr. Topic Med. Chem., 2022, 22(6), 473-492.
[67]
Mathew, B.; Koyimparambath, V.P.; Oh, J.M.; Khames, M.A.; Nair, A.S.; Nath, L.R. Trimethozylated halogenated chalcones as dual inhibitors of MAO-B and BACE-1 for treatment of neurodegenerative disorders. Pharmaceutics, 2021, 13, 1-16.
[68]
Rehuman, N.A.; Oh, J.M.; Nath, L.R.; Khames, A.; Abdelgawad, M.A.; Gambacorta, N.; Nicolotti, O.; Jat, R.K.; Kim, H.; Mathew, B. Halogenated Coumarin–Chalcones as Multifunctional Monoamine Oxidase-B and Butyrylcholinesterase Inhibitors. ACS Omega, 2021, 6(42), 28182-28193.
[http://dx.doi.org/10.1021/acsomega.1c04252] [PMID: 34723016]